Biocatalysis in Deep Eutectic Solvents

Biocatalysis in deep eutectic solvents (DESs) has emerged as a versatile and sustainable approach to drive enzyme‐mediated transformations under non‐conventional conditions. DESs are eutectic mixtures of hydrogen‐bond donors and salts that display low volatility, tunable polarity and exceptional biocompatibility. These solvents enable enhanced enzyme stability, altered substrate solubility and modulated reaction equilibria. The intricate hydrogen‐bond network within a DES can stabilise non‐native protein conformations or preserve catalytic activity at elevated temperatures, while controlled addition of water adjusts viscosity and mass‐transfer properties. Applications span asymmetric reductions, oxidations, transesterifications and the synthesis of fine chemicals and biopolymers. By replacing volatile organic solvents and ionic liquids with DESs, researchers are advancing greener routes to pharmaceuticals, surfactants and biomaterials. Challenges include the high intrinsic viscosity of many DESs, substrate accessibility and the critical role of hydration in enzyme performance. Ongoing efforts focus on tailoring DES composition, combining DESs with co‐solvents or ionic liquids, and designing natural deep eutectic solvents (NADESs) to broaden the scope and efficiency of biocatalytic processes.

Research from Nature Portfolio

One foundational study demonstrated that a biphasic system combining a choline chloride–ethylene glycol deep eutectic solvent with a water‐immiscible ionic liquid markedly improved the whole‐cell biocatalytic reduction of 2-octanone. In this system, the DES component increased cell membrane permeability, raising the optimal substrate concentration from 40 mM to 60 mM, while the ionic liquid phase allowed substrate loading up to 1.5 M. The reduction of 2-octanone to (R)-2-octanol proceeded with over 99.9 % enantiomeric excess. Cells retained high operational stability over multiple cycles, illustrating the synergistic interplay of DES and ionic liquid phases in enhancing reaction rates, enantioselectivity and catalyst reuse, and setting a benchmark for solvent‐engineered asymmetric bioreductions.

Biocatalysis in Deep Eutectic Solvents publication trend

The graph below shows the total number of articles in biocatalysis in deep eutectic solvents across all publications each year (not limited to Nature Index journals).

Technical terms

Deep eutectic solvent (DES): A eutectic mixture of a hydrogen‐bond donor and a salt that forms a liquid with melting point lower than either component, featuring low volatility and high biocompatibility.

Biocatalysis: The acceleration of chemical reactions by enzymes or whole cells, offering high selectivity under mild conditions.

Natural deep eutectic solvent (NADES): A subclass of DESs derived from naturally occurring metabolites, designed for enhanced enzyme compatibility and environmental friendliness.

Two‐phase system: A reaction medium composed of two immiscible liquid phases that partition substrates, products and catalysts to optimise reaction efficiency and separation.

References

1. Recent progress on deep eutectic solvents in biocatalysis. Bioresources and Bioprocessing (2017).
2. Combination of deep eutectic solvent and ionic liquid to improve biocatalytic reduction of 2-octanone with Acetobacter pasteurianus GIM1.158 cell. Scientific Reports (2016).
3. Stabilization of Non-Native Folds and Programmable Protein Gelation in Compositionally Designed Deep Eutectic Solvents. ACS Nano (2024).
4. Malic acid-based deep eutectic solvent and its application in Insulin's structural stability. Results in Engineering (2023).
5. Deep Eutectic Solvents for the Enzymatic Synthesis of Sugar Esters: A Generalizable Strategy?. ACS Sustainable Chemistry & Engineering (2023).